Planar cell polarity enables posterior localization of nodal cilia and left-right axis determination during mouse and Xenopus embryogenesis.
Planar cell polarity enables posterior localization of nodal cilia and left-right axis determination during mouse and Xenopus embryogenesis.
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DOI：
10.1371/journal.pone.0008999
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发表时间：
2010-02-02
期刊：
影响因子：
3.7
通讯作者：
Axelrod JD
中科院分区：
文献类型：
--
作者：
Antic D;Stubbs JL;Suyama K;Kintner C;Scott MP;Axelrod JD
脊椎动物的左右不对称始于人类和小鼠的腹侧结节和青蛙的胃腔顶板(GRP)的早期胚胎结构。在这些结构中，每个上皮细胞都有一个可移动的纤毛，这些纤毛的协同跳动产生了向左流动的液体，这是启动左右不对称基因表达所必需的。向左的液体流动被认为是纤毛向后倾斜的结果，纤毛从每个细胞顶端表面的后部附近伸出。因此，这些细胞表现出形态上的平面极化。平面细胞极化(PCP)表现为细胞在上皮片内的协调、极化取向，或细胞在融合延伸过程中的定向迁移和嵌插。一组进化上保守的蛋白质调节PCP。在这里，我们提供了脊椎动物PCP蛋白调节小鼠腹侧结节和非洲爪哇胃腔顶板平面极性的证据。VANGL1和PRICKLE2(PK2)在小鼠腹结节细胞中的不对称前部定位表明，这些细胞是由保守的分子机制平面极化的。弱穿透性Vangl1突变表型提示，Vangl1功能受损可能与左右侧畸形有关。更有力的功能证据来自非洲爪哇GRP，我们发现Vangl2蛋白功能的扰动扰乱了向左流动所需的活动纤毛的后部定位，并导致左侧特异基因Nodal的异常表达。在小鼠和非洲爪哇胚胎组织者中观察到的前后部PCP反映了这一机制的强烈进化保守，这对身体计划的确定很重要。
Left-right asymmetry in vertebrates is initiated in an early embryonic structure called the ventral node in human and mouse, and the gastrocoel roof plate (GRP) in the frog. Within these structures, each epithelial cell bears a single motile cilium, and the concerted beating of these cilia produces a leftward fluid flow that is required to initiate left-right asymmetric gene expression. The leftward fluid flow is thought to result from the posterior tilt of the cilia, which protrude from near the posterior portion of each cell's apical surface. The cells, therefore, display a morphological planar polarization. Planar cell polarity (PCP) is manifested as the coordinated, polarized orientation of cells within epithelial sheets, or as directional cell migration and intercalation during convergent extension. A set of evolutionarily conserved proteins regulates PCP. Here, we provide evidence that vertebrate PCP proteins regulate planar polarity in the mouse ventral node and in the Xenopus gastrocoel roof plate. Asymmetric anterior localization of VANGL1 and PRICKLE2 (PK2) in mouse ventral node cells indicates that these cells are planar polarized by a conserved molecular mechanism. A weakly penetrant Vangl1 mutant phenotype suggests that compromised Vangl1 function may be associated with left-right laterality defects. Stronger functional evidence comes from the Xenopus GRP, where we show that perturbation of VANGL2 protein function disrupts the posterior localization of motile cilia that is required for leftward fluid flow, and causes aberrant expression of the left side-specific gene Nodal. The observation of anterior-posterior PCP in the mouse and in Xenopus embryonic organizers reflects a strong evolutionary conservation of this mechanism that is important for body plan determination.
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影响因子：
5.3
作者：
Montcouquiol, Mireille;Sans, Nathalie;Kelley, Matthew W.
通讯作者：
Kelley, Matthew W.
影响因子：
4.5
作者：
Etheridge SL;Ray S;Li S;Hamblet NS;Lijam N;Tsang M;Greer J;Kardos N;Wang J;Sussman DJ;Chen P;Wynshaw-Boris A
通讯作者：
Wynshaw-Boris A
影响因子：
9.8
作者：
Nonaka S;Yoshiba S;Watanabe D;Ikeuchi S;Goto T;Marshall WF;Hamada H
通讯作者：
Hamada H
影响因子：
9.2
作者：
Schweickert, Axel;Weber, Thomas;Blum, Martin
通讯作者：
Blum, Martin
DOI：
10.1016/j.cub.2009.04.018
发表时间：
2009-06-09
期刊：
Current biology : CB
影响因子：
--
作者：
Mitchell B;Stubbs JL;Huisman F;Taborek P;Yu C;Kintner C
通讯作者：
Kintner C